Narrow particle size distribution porous microspheres and method of making the same

ABSTRACT

Porous polymer microspheres having a size of from about 3 to about 50 microns and a geometric standard deviation of about 1.25 or less are disclosed. The porous polymer microspheres are made by a method including the steps of preparing an emulsion comprised of polymer particles having an average particle size of less than about 3 microns and a diluent, subjecting the emulsion to an aggregating condition to form aggregated polymer particles, optionally coalescing the aggregated polymer particles, and removing the diluent to form the porous polymer microspheres.

BACKGROUND

Described herein are porous microspheres having a size of from about 3to about 50 microns and a narrow particle size distribution. Alsodescribed is an emulsion aggregation method for making such porousmicrospheres.

There are numerous applications for porous microspheres in chemistry,biochemistry and environmental engineering, including use inion-exchangers, adsorbents and separation media. There is also asignificant amount of biochemical research that benefits from the use ofporous microspheres.

There has been an increasing interest in porous polymer particles inrecent years. Especially, styrene-acrylate copolymers have been used asprecursors for ion-exchangers, adsorbents and GPC column materials.Crosslinked polymer particles with a permanent macroporous structure areefficient materials for many separation processes. The macropores of theparticles allow biomolecules, for example in the general size of 500,000dalton, to be separated.

The preparation of porous microspheres in the size range of about 3 toabout 50 microns with narrow particle size distributions is oftendifficult and expensive. Existing methods of preparing these materialsare limited and often involve the use of size classification. Sizeclassification is time consuming and wasteful, as a large percentage ofthe microspheres must be discarded as being too large or too small.

Porous polymer microspheres may be produced by suspension polymerizationby adding an inert diluent to the polymerizing mixture. Afterpolymerization, the inert diluent is removed, leaving a porous structurewithin the polymer particles. The suspension process gives relativelylarge particles (100-10,000 μm) with a broad particle size distribution,which is disadvantageous with regards to flow conditions, separation andpacking efficiency. It is expected that the improved separationefficiency, optimal packing and lower backpressure can be achieved withnarrower particle size distribution macroporous polymer particles ascompared to polydisperse separation media.

U.S. Pat. No. 6,841,580 describes an organic porous material having acontinuous pore structure, which comprises interconnected macropores andmesopores with a radius of 0.01 to 100 microns in the walls of themacropores, having a total pore volume of 1 to 50 ml/g and having poredistribution curve characteristics wherein the value obtained bydividing the half-width of the pore distribution curve at the main peakby the radius at the main peak is 0.5 or less. The organic porousmaterial is useful as an adsorbent having high physical strength andexcelling in adsorption amount and adsorption speed, an ion exchangerexcelling in durability against swelling and shrinkage, and a filler forchromatography exhibiting high separation capability. See the Abstract.

A simple and economical process for preparing porous microspheres in thesize range of from about 3 to about 50 microns that allows for controlof size distribution is desired.

SUMMARY

What is sought, then, is an economical process for preparing narrowparticle size distribution porous polymer particles in the size range ofabout 3 to about 50 microns. Such process would be very beneficial to atleast ion-exchange, adsorbent, chromatography, bioprocessing,immobilized enzyme, drug delivery and catalysis fields.

In embodiments, described are porous polymer microspheres having a sizeof from about 3 to about 50 microns and a geometric standard deviationof about 1.25 or less.

In further embodiments, described are porous polymer microspherescomprised of emulsion aggregated crosslinked styrene-acrylate polymerand having a size of from about 3 to about 50 microns and a geometricstandard deviation of about 1.25 or less.

In still further embodiments, described is a method of making porouspolymer microspheres having an average size of from about 3 to about 50microns and a geometric standard deviation of about 1.25 or less,comprising preparing an emulsion comprised of polymer particles havingan average particle size of less than about 3 microns and a diluent,subjecting the emulsion to an aggregating condition to form aggregatedpolymer particles, optionally coalescing the aggregated polymerparticles, and removing the diluent to form the porous polymermicrospheres.

BRIEF DESCRIPTION OF THE DRAWING

The FIGURE is an SEM micrograph of 8.5 μm, narrow size distributionporous microspheres prepared by an emulsion aggregation process.

DETAILED DESCRIPTION OF EMBODIMENTS

The porous polymer microspheres having a narrow particle sizedistribution and an average particle size of about 3 to about 50 micronsare prepared by an emulsion aggregation (EA) process.

In embodiments, the process includes the steps of preparing an emulsioncomprised of polymer particles having an average particle size of lessthan about 3 microns and a diluent, subjecting the emulsion to anaggregating condition to form aggregated polymer particles, optionallycoalescing the aggregated polymer particles, and removing the diluent toform the porous polymer microspheres.

The emulsion of small sized polymer particles and diluent may beprepared by any suitable means without limitation. In embodiments, theemulsion is prepared by mixing a latex of the small sized polymerparticles with an emulsion of the diluent.

The polymeric materials may be synthesized such that they are formed asemulsions in water or can be turned into emulsions in water thoughprocesses of heating in water, with or without surfactants or otherstabilizers. The latex of small sized polymer particles may be derivedvia conventional emulsion polymerization techniques, although othertechniques of preparing and/or dispersing the small sized polymerparticles to form the latex may be used, for example polymermicrosuspension and the like. In emulsion polymerization, one or moremonomers are emulsified and then polymerized to form the small sizedpolymer particles as a latex. These small sized polymer particles willbe aggregated to form the larger porous polymer particles. Thus, thesmall sized particles should have an average particle size less than 3microns. For example, the small sized particles have an average size offrom, for example, about 5 nm to about 1,000 nm.

The monomers used to form the polymer particles are not particularlylimited. Suitable example monomers include styrene, acrylates,methacrylates, butadiene, isoprene, and optionally acid or basicolefinic monomers, such as acrylic acid, methacrylic acid, acrylamide,methacrylamide, quaternary ammonium halide of dialkyl or trialkylacrylamides or methacrylamides, vinylpyridine, vinylpyrrolidone,vinyl-N-methylpyridinum chloride and the like, and mixtures thereof. Thepresence of acid or basic groups in the monomers is optional, and suchgroups can be present in various amounts of from, for example, about 0.1to about 10 percent by weight of the polymer resin. In embodiments, themonomer includes a mixture of styrene and acrylate monomers such thatthe polymer is a styrene acrylate.

In embodiments, the polymer particles are crosslinked. This may be doneby including one or more crosslinking monomers in the emulsion.Crosslinking monomers may include, for example, divinylbenzene ordiethylene glycol methacrylate. The crosslinking monomer(s) may beincluded in effective amounts, for example from about 1 to about 20percent by weight of the polymer resin.

In addition, chain transfer agents, for example dodecanethiol,water-soluble thiols such as butanethiol or propanethiol, or carbontetrabromide, may also be included in the monomer emulsion, if desired,in order to control the molecular weight properties of the polymer. Ifpresent, the chain transfer agent(s) may be included in amounts of, forexample, about 1 to about 10 percent by weight of the polymer resin.

The latex polymer particles derived may be comprised of a polymerselected from the group consisting of poly(styrene-alkyl acrylate),poly(styrene-1,3-diene), poly(styrene-alkyl methacrylate),poly(styrene-alkyl acrylate-acrylic acid),poly(styrene-1,3-diene-acrylic acid), poly(styrene-alkylmethacrylate-acrylic acid), poly(alkyl methacrylate-alkyl acrylate),poly(alkyl methacrylate-aryl acrylate), poly(aryl methacrylate-alkylacrylate), poly(alkyl methacrylate-acrylic acid), poly(styrene-alkylacrylate-acrylonitrile-acrylic acid),poly(styrene-1,3-diene-acrylonitrile-acrylic acid), poly(alkylacrylate-acrylonitrile-acrylic acid, poly(methylstyrene-butadiene),poly(methyl methacrylate-butadiene), poly(ethyl methacrylate-butadiene),poly(propyl methacrylate-butadiene), poly(butyl methacrylate-butadiene),poly(methyl acrylate-butadiene), poly(ethyl acrylate-butadiene),poly(propyl acrylate-butadiene), poly(butyl acrylate-butadiene),poly(styrene-isoprene), poly(methylstyrene-isoprene), poly(methylmethacrylate-isoprene), poly(ethyl methacrylate-isoprene), poly(propylmethacrylate-isoprene), poly(butyl methacrylate-isoprene), poly(methylacrylate-isoprene), poly(ethyl acrylate-isoprene), poly(propylacrylate-isoprene), poly(butyl acrylate-isoprene), poly(styrene-propylacrylate), poly(styrene-butyl acrylate), poly(styrene-butadiene-acrylicacid), poly(styrene-butadiene-methacrylic acid),poly(styrene-butadiene-acrylonitrile-acrylic acid), poly(styrene-butylacrylate-acrylic acid), poly(styrene-butyl acrylate-methacrylic acid),poly(styrene-butyl acrylate-acrylononitrile), poly(styrene-butylacrylate-acrylononitrile-acrylic acid), and the like. Poly(styrene-alkylacrylates) is desirably used.

The emulsion polymerization process is well known, and need not befurther described herein. Several U.S. patents describe suitableemulsion polymerization techniques. See, for example, U.S. Pat. No.5,853,943, incorporated herein by reference in its entirety.

As the emulsifier or surfactant selected for the preparation of thelatex, such may be of the formula

wherein R₁ or R₂ is hydrogen, or alkyl with, for example, from about 1to about 25 carbons such as from about 6 to about 16 carbon atoms, and Mis hydrogen, an alkali metal such as sodium or potassium, or ammonium(NH₄), with the emulsifier being sodium tetrapropyl diphenyloxidedisulfonate. For sodium n-decyl diphenyloxide disulfonate, R₁ ishydrogen, R₂ is a n-decyl group, and M is sodium. Examples of specificemulsifiers include sodium hexyl diphenyloxide disulfonate, sodiumn-decyl diphenyloxide disulfonate, sodium n-dodecyl diphenyloxidedisulfonate, sodium n-hexadecyl diphenyloxide disulfonate, sodiumpalmityl diphenyloxide disulfonate, n-decyl diphenyloxide disulfonicacid, n-dodecyl diphenyloxide disulfonic acid, and tetrapropyldiphenyloxide disulfonic acid. The emulsifiers or surfactants includediphenyloxide disulfonates, such as DOWFAX 2A1™, DOWFAX 3A2™, DOWFAX8390™ available Dow Chemical, RHODACAL DSB™ available fromRhone-Poulenc, POLY-TERGENT 2A1™, POLY-TERGENT 2EP™ available from Olin,AEROSOL DPOS-45™ available from Cytec, CALFAX DBA-40™, CALFAX 16L-35™available from Pilot Chemicals, and the like. Diphenyloxide disulfonateemulsifiers represent a class of highly anionic surface active agentsconsisting of disulfonated alkyl diphenyl oxide molecules in which thecharge arises from two sulfonate groups rather than one as in themajority of surfactants (such as dodecylbenzene sulfonate), providesexcellent emulsion stability. Diphenyloxide disulfonates also possesshigh oxidation resistance and high temperature stability up to, forexample, 95° C., rendering them suitable for use in emulsionpolymerization.

A diluent is added to the emulsion of small sized particles. The diluentshould be inert to reaction with the polymer particles. The diluent willoccupy areas within the aggregated polymer particles, thereby creatingthe macropores of the polymer particles upon removal of the diluent.

The diluents used are solvating or nonsolvating diluents (solvent ornon-solvent) for polymer chains, or inert linear polymer. Examples ofthe inert diluents that may be used in the method include benzene,toluene, ethylbenzene, xylene, methylene chloride, ethylene chloride,n-hexane, n-heptane, i-octane, nonane, decane, dodecane, hexadecane,cyclohexane, 1-pentanol, 1-hextanol, 1-heptanol, 1-octanol, 1-decanol,1-dodecanol, and the like.

In embodiments, the diluent is added as an emulsion. The chemicallydispersed diluent emulsion is comprised of diluent and dispersant,wherein the dispersant is nonionic, ionic or a mixture of surfactants,for example, anionic DOWFAX 2A1™ and nonionic poly(N-vinylpyrrolidone)).

A sufficient amount of diluent is added to the polymer particle latexsuch that the ultimate particles will have a porosity of, for example,about 10% to about 75%, such as from about 30% to about 50%. The ratioof diluent to polymer particles on a weight basis may be, for example,about 0.3 to about 3 to 1, such as from about 0.5 to about 2 to 1.

The emulsion of polymer particles and diluent is then subjected to anaggregation condition in order to aggregate the small sized polymerparticles into larger sized polymer particles. In general, theaggregating condition includes at least the addition of an aggregatingagent or coagulant to the emulsion. As the aggregating agent, mentionmay be made of a metal salt, a polymeric salt, or an ionic material thatwould cause flocculation and aggregation of the polymer particles.Specific non-limiting examples include polyaluminum halides such aspolyaluminum chloride (PAC), or the corresponding bromide, fluoride, oriodide, polyaluminum silicates such as polyaluminum sulfo silicate(PASS), and water soluble metal salts including aluminum chloride,aluminum nitrite, aluminum sulfate, potassium aluminum sulfate, calciumacetate, calcium chloride, calcium nitrite, calcium oxylate, calciumsulfate, magnesium acetate, magnesium nitrate, magnesium sulfate, zincacetate, zinc nitrate, zinc sulfate and the like.

The aggregating agent may be added to the emulsion in bulk, or may bemetered in during aggregation. The aggregating agent may be added in anamount of about 0.05 pph to about 5 pph of the polymer. More inparticular, in embodiments, the aggregating agent is added in amounts offrom about 0.01 to about 5% by weight of the polymer, such as from about0.5 to about 2.5% by weight of the polymer.

Additional aggregating conditions may include application of heat andcontrol of mixing and pH conditions.

For example, the growth and shaping of the particles following additionof the aggregating agent may be accomplished under conditions in whichaggregation occurs separate from coalescence or conditions under whichaggregation and coalescence occur continuously together. For separateaggregation and coalescence particle formation steps, the aggregationmay be conducted under shearing conditions (for example, mixing at about100 to about 5,000 revolutions per minute using any suitable device andequipment, for example, using an IKA ULTRA TURRAX T50 probe homogenizer)at a temperature of from about 25° C. to about 75° C. For example, thepolymer particles are aggregated at a temperature below the glasstransition (Tg) temperature of the polymer, for example at a temperatureof from about 15° C. to about 1° C. below the Tg of the polymerparticles. Following aggregation to the desired particle size, theparticles may optionally be coalesced to a desired final shape,coalescence being used to render the particles more spherical.Coalescence may be effected by heating the mixture to a temperature offrom about 75° C. to about 115° C. Coalescence may also be conductedwith lowering the pH to about 1.5 to about 6.0, such as lowering the pHto about 2.5 to about 5.5, with an acid.

When the aggregation is effected at substantially the same time theparticles are being coalesced, then the mixture is may be heated toabout 75° C. to about 115° C.

The particles are permitted to aggregate until a predetermined desiredparticle size is obtained. The particle size may be monitored during thegrowth process until such particle size is reached. Samples may be takenduring the growth process and analyzed, for example with a CoulterCounter, for average particle size. Once the predetermined desiredparticle size is reached, then the growth process is halted. Inembodiments, the predetermined desired particle size is within the rangeof about 3 to about 50 microns, such as from about 5 to about 20microns.

Upon the particles reaching the predetermined desired particle size,further growth of the particles is halted. This may be done by, forexample, adjusting the pH or adding an agent that scavenges remainingaggregating agent. For example, when the aggregates approach therequired size, such as from about 3 to about 50 microns in volumeaverage diameter, growth may be hindered through adjustment of the pH,for example to about 4.0 to about 9.0, more particularly to about 5.0 toabout 6.5, with a known caustic agent such as sodium hydroxide.

Once the microspheres have the desired size and shape, the particleslurry is cooled to an appropriate working temperature, such as 30° C.,more particularly, the temperature is about 10° C. to about 50° C. Then,the inert diluent is removed from the polymer particles. The removal maybe effected by subjecting the polymer microspheres to extraction withnon-solvent such as methanol, for example in a Soxhlet apparatus, for aperiod of time, for example for about 1 to 36 hours, to remove the inertdiluent. Other non-solvents that may be used include, but are notlimited to, ethanol, 2-propanol, 2-methoxyethanol, 2-ethoxyethanol,acetic acid, acetone, and the like. During the extraction process, themicrospheres are added to the non-solvent at low concentration, forexample at a microsphere to non-solvent ratio of 5% or less.

Once the diluent is removed to generate the porous polymer particles,the polymer particles are optionally washed with water, for example toremove residual non-solvent and other impurities, surfactants, and thelike, and dried.

The polymer particles achieved are thus porous, and have an average sizeof from about 3 to about 50 microns and a narrow particle sizedistribution. Such narrow particle size distribution porous microsphereshave been applied in size exclusion chromatography. The particles givesuperior efficiency in packing, speed, and resolution as compared withsystems using wide particle size distribution particles.

The particle size of the porous microspheres is thus about 3 to about 50microns, such as about 5 to about 20 microns. The particle sizedistribution (geometric standard deviation) is desirably less than 1.25,such as from about 1.15 to about 1.25, as determined by a Layson Cellparticle analyzer. The emulsion aggregation technique permits the porousparticles to have such size and narrow particle size distributionwithout the need for time consuming and expensing post-processing of theparticles.

The porous microspheres may have an average pore size larger than 500 Åin diameter, a pore volume of about 0.4 to about 0.7 ml/g, and aporosity of about 30 to about 50%, as determined by mercury intrusionporosimetry. Further, the porous microspheres also have internal surfaceareas in the 15 to about 60 m²/g range, for example as determined by theBrunauer, Emmett and Teller (BET) method.

The porous microspheres in embodiments may optionally contain monomersthat result in the presence of functional groups on the surface of themicrospheres formed, and/or further chemical treatment of themicrospheres may be performed to create such functional groups on thesurface. Such functional groups can be useful to enable the covalentbonding or complexation of radioactive materials, biological materials,or ligands for attaching radioactive or biological materials. Assuitable monomers and surface treatment materials that provideappropriate functional groups, mention may be made of functionalmonomers such as styrene, vinyltoluene, sulfonated styrene, methylmethacrylate, ethyl methacrylate, 2-hydroxyethyl acrylate,2-hydroxyethyl methacrylate, vinyl acetate, acrylic acid, methacrylicacid, β-carboxyethyl acrylate, acrylamine, methacrylamide, quartenaryammonium halide of dialkyl or trialkyl acrylamides or methacrylamides,vinylpyridine, vinylpyrrolidone and vinyl-N-methylpyridinum, andmixtures thereof.

Post-copolymerization of functional monomers with residual double bondsof porous polymer microspheres containing divinylbenzene or diethyleneglycol methacrylate may also be used for grafting functional groups,provided the grafted monomer is copolymerized with styrene oracrylate-like units. The functional groups grafted on the surface can be—C—O—, —C═O, —O—C═O, —C—O—O, —C—N, —C═N, —C≡N, —NH, —NH₂, —CF, —CF₂,—CF₃, or —SO₃. These double bonds should be at least partly reacted, forexample undergoing cationic polymerization during chloromethylation bychloromethylether in the presence of Friedel-Crafts catalysts.

The FIGURE is an SEM micrograph of an 8.5 μm narrow size distributionporous crosslinked styrene-acrylate polymer microsphere prepared by theemulsion aggregation process. N-heptane was used as inert diluent.Divinylbenzene in an amount of 10 wt % is used to prepare thecrosslinked styrene-acrylate polymer. The GSD of the porous microspheresis about 1.18, as determined by the Layson Cell particle analyzer. Theporous microspheres possess an average pore size of 560 A in diameter, apore volume of 0.62 ml/g, and a porosity of 44%, as determined bymercury intrusion porosimetry. The porous microspheres have internalsurface areas of 54 m²/g as determined by BET method.

Embodiments are further illustrated by way of the following non-limitingexamples.

EXAMPLE 1 Crosslinked Polymer Latex Synthesis

This example illustrates a method of preparing a poly(styrene-butylacrylate-β-carboxyethyl acrylate-divinylbenzene) polymer latex.

A polymer latex (EP611) comprised of a styrene/n-butylacrylate/β-carboxyethyl acrylate/divinylbenzene copolymer of 74:13:3:10prepared with 1.7 pph dodecanethiol (chain transfer agent), 0.35 pphbranching agent (A-DOD, decanediol diacrylate, available fromShin-Najamura Co., Japan) and 1.5 percent of ammonium persulfateinitiator was synthesized by a semicontinuous emulsion polymerizationprocess using the anionic surfactant DOWFAX 2A1™ (sodium tetrapropyldiphenoxide disulfonate, 47 percent active, available from DowChemical).

In a 3 gallon jacketed stainless steel reactor with double flightimpellers (a four pitched-blade impeller each) set at 35 rpm, 3.87kilograms of deionized water with 5.21 grams of DOWFAX 2A1™ (7 percentof the total surfactant) was charged while the temperature was raisedfrom room, about 23 to about 25° C., to 80° C. A monomer emulsion wasprepared by mixing a monomer mixture (3,105 grams of styrene, 545 gramsof n-butyl acrylate, 126 grams of β-carboxyethyl acrylate (β-CEA), and420 grams of divinylbenzene (55% active, available from Dow Chemical)),14.3 grams of A-DOD and 45 grams of 1-dodecanethiol with 1,930 grams ofdeionized water and 80.7 grams of DOWFAX 2A1™ (93 percent of the totalsurfactant) at room temperature for 30 minutes in a 1.5 gallon Popetank. 63 grams of the seed were pumped from the monomer emulsion into a0.2 gallon beaker and subsequently the seed was charged into the reactorat 80° C. An initiator solution prepared from 61 grams of ammoniumpersulfate in 302 grams of deionized water was added over 20 minutesafter the seed emulsion addition. The reactor was stirred at 48 rpm foran additional 20 minutes to allow seed particle formation at 80° C. Themonomer emulsion was then fed into the reactor. Monomer emulsion feedingwas stopped after 110 minutes and 24.9 grams of 1-dodecanethiol (DDT)were added to the remaining emulsion in the 1.5 gallon Pope tank whichwas mixed for a further 5 minutes before feeding resumed. The remainingmonomer emulsion was fed into the reactor over 90 minutes. At the end ofthe monomer feed, the emulsion was post-heated at 80° C. for 180minutes, then cooled to 25° C. The reaction system was deoxygenated bypassing a stream of nitrogen through it during the reaction.

A latex resin containing 42 weight percent styrene-butylacrylate-β-carboxyethyl acrylate-divinylbenzene resin, 57 weight percentwater, 0.4 weight percent anionic surfactant DOWFAX 2A1™, and 0.6percent of an ammonium sulfate salt species was obtained. The resultingcrosslinked polymer poly(styrene-butyl acrylate-acrylicacid-β-carboxyethyl acrylate-divinylbenzene) possessed a mid-point Tg of70.7° C., as measured on a Seiko DSC. The latex resin or polymerpossessed a volume average diameter of 252 nanometers as measured bylight scattering technique on a Coulter N4 Plus Particle Sizer.

EXAMPLE 2 Diluent Emulsion Preparation

An aqueous diluent emulsion (DE742) containing n-heptane and asurfactant in water is generated using a homogenization process. 300grams of n-heptane, 218.8 grams of a surfactant aqueous solutioncontaining 27.0 grams of the anionic surfactant DOWFAX 2A1™, and 981grams of deionized water are dispensed into a beaker and stirred withthe aid of a mechanical stirrer to mix the dry pigment powder, water andDOWFAX 2A1™ solution mixture. The resultant diluent mixture ispredispersed for about 5 minutes using an IKA ULTRA TURRAX® T50homogenizer (IKA Labortechnik, Germany) operating at a speed starting atabout 4,000 revolutions per minute and ending at about 7,000 revolutionsper minute. The resulting predispersed diluent mixture is then pouredinto the feed hopper of a Rannie Lab 2000 homogenizer (APV HomogenizerGroup, USA).

The homogenizer is activated to pump the polymer mixture through thehomogenizer at a rate of about 11 liters per hour. The product iscollected in a product container wherein the container is cooled bymeans of an ice bath. Initially, the homogenizer primary and secondaryvalves are kept fully open. When the diluent mixture is being pumpedsteadily through the homogenizer, the homogenizer primary valve isclosed to increase the pressure drop in the valve to about 50megapascals. When the feed hopper is nearly empty, the homogenizedproduct in the product container is poured back into the feed hopper,and the homogenizer primary valve is further closed to increase thepressure drop in the valve to a final set point of about 150megapascals. In total, the diluent mixture was pumped through thehomogenizer 28 times at a pressure of 150 megapascals. At the completionof homogenization, the homogenizer primary valve is opened and thehomogenizer is disengaged.

The product is comprised of a surfactant stabilized diluent emulsioncomprising 20.5 weight percent of n-heptane, 1.85 weight percent ofDOWFAX 2A1™ surfactant, and 77.65 weight percent of water. The diluentemulsion has a volume median diameter of 312 nanometers as measured bylight scattering technique on a Coulter N4 Plus Particle Sizer.

EXAMPLE 3 Narrow Size Porous Polymer Microsphere Preparation

This example illustrates preparation of 8.5 micron narrow size porouspolymer microspheres generated by PAC aggregation/coalescence.

The poly(styrene-butyl acrylate-β-carboxyethyl acrylate-divinylbenzene)polymer latex of Example 1 (EP611) and diluent emulsion of Example 2(DE742) above were utilized in an aggregation/coalescence (A/C) processto produce 8.5 micron (volume average diameter) particles with a narrowsize distribution.

500 grams of deionized water was placed in a stainless steel beaker andhomogenized at 5,000 rpm, while there was added 300 grams of latexpoly(styrene-butyl acrylate-β-carboxyethyl acrylate-divinylbenzene)(EP611), followed by the addition of 292 grams of diluent emulsion(DE742). To the resulting homogenized latex/diluent blend, 2.4 grams of10 percent PAC (polyaluminum chloride obtained from Asada Company ofJapan) solution diluted with 24 grams of 0.02N HNO₃ was added dropwiseto cause a flocculation of the crosslinked polymer latex and then-heptane diluent emulsion. After the addition was complete,homogenization was continued for an additional 2 minutes to form acreamy blend with an average particle size by volume of 2.53 and with aGSDv of 1.20.

The creamy blend was then transferred into a 2 liter glass reactor andstirred at 350 rpm, while being heated to about 62° C. to about 63° C.Particle growth was monitored during heating. When the particle sizediameter of the solids by volume was equal to 8.8 (GSDv=1.18), the pH ofthe slurry was adjusted. The pH was adjusted to 7.5 by the addition of a2 percent NaOH solution and the speed in the reactor was reduced to 200rpm. After ½ hour of stirring at 63° C., the temperature in the reactorwas increased to 83° C. After 1 hour of heating at 83° C., the pH of theslurry was adjusted to 4.3 and the heating was continued for anadditional 10 hours. Thereafter, the reactor contents were cooled downto about room temperature, about 23° C. to about 25° C., and weredischarged.

A 16 percent solids slurry of 8.6 micron polymer microspheres withGSDv=1.19 was obtained. The resulting polymer microsphere product wascomprised of about 31 percent of n-heptane, about 0.2 weight percent ofPAC and about 68.8 percent by weight of the resin poly(styrene-butylacrylate-β-carboxyethyl acrylate-divinylbenzene), and the total amountof the polymer microsphere components was about 100 percent.

After emulsion/aggregation process, the polymer microspheres wereextracted with methanol (a non-solvent for polystyrene) in a Soxhletapparatus for 24 hours to remove the inert diluent (n-heptane), followedby washing with water to remove residual methanol. During the extractionprocess, the microspheres were added to methanol at low concentration(microsphere/methanol ratio of about 5%). The resulting porousmicrospheres are then washed with water to remove impurities,surfactants, etc., and dried at room temperature (about 23° C.).

The resulting 8.5 μm narrow size distribution porous microspheres wereprepared by the EA (emulsion aggregation) process, by the use ofn-heptane as inert diluent. The GSD the porous microspheres is about1.18, as determined by the Layson Cell particle analyzer. The porousmicrospheres possess an average pore size of 560 Å in diameter, a porevolume of 0.62 ml/g, and a porosity of 44%, as determined by mercuryintrusion porosimetry on a Micrometritics AutoPore 9200 porosimeter(Micrometritics Co.). The porous microspheres have internal surfaceareas of 54 m²/g as determined by Brunauer, Emmett and Teller (BET)method in a Quantasorb Sorption System (Quantachrome Corp., Model OS-9).

It will be appreciated that various of the above-disclosed and otherfeatures and functions, or alternatives thereof, may be desirablycombined into many other different systems or applications. Also,various presently unforeseen or unanticipated alternatives,modifications, variations or improvements therein may be subsequentlymade by those skilled in the art, and are also intended to beencompassed by the following claims.

1. Porous polymer microspheres having a size of from about 3 to about 50microns and a geometric standard deviation of about 1.25 or less.
 2. Theporous polymer microspheres according to claim 1, wherein themicrospheres have an average pore size of at least about 500 Å.
 3. Theporous polymer microspheres according to claim 1, wherein themicrospheres have a pore volume of about 0.4 to about 0.7 ml/g.
 4. Theporous polymer microspheres according to claim 1, wherein themicrospheres have a porosity of about 30 to about 50%.
 5. The porouspolymer microspheres according to claim 1, wherein the microspheres haveinternal surface areas of from about 15 to about 60 m²/g.
 6. The porouspolymer microspheres according to claim 1, wherein the microspheres arecomprised of polymer of one or more of styrene, acrylates,methacrylates, butadiene, isoprene, acrylic acid, methacrylic acid,acrylamide, methacrylamide, quartenary ammonium halide of dialkyl ortrialkyl acrylamides or methacrylamides, vinylpyridine, vinylpyrrolidoneand vinyl-N-methylpyridinum.
 7. The porous polymer microspheresaccording to claim 6, wherein the polymer is crosslinked.
 8. The porouspolymer microspheres according to claim 1, wherein the microspheres havea size of from about 5 to about 20 microns and a geometric standarddeviation of about 1.15 to about 1.25.
 9. The porous polymermicrospheres according to claim 1, wherein the porous polymermicrospheres are emulsion aggregated.
 10. The porous polymermicrospheres according to claim 1, wherein the microspheres havefunctional groups on surfaces thereof.
 11. The porous polymermicrospheres according to claim 10, wherein the functional groups on thesurfaces comprise —C—O, —C═O, —O—C═O, —C—O—O, —C—N, —C═N, —C≡N, —NH,—NH₂, —CF, —CF₂, —CF₃, or —SO₃.
 12. The porous polymer microspheresaccording to claim 10, wherein the functional groups on the surfaces arederived from styrene, vinyltoluene, sulfonated styrene, methylmethacrylate, ethyl methacrylate, 2-hydroxyethyl acrylate,2-hydroxyethyl methacrylate, vinyl acetate, acrylic acid, methacrylicacid, β-carboxyethyl acrylate, acrylamine, methacrylamide, quartenaryammonium halide of dialkyl or trialkyl acrylamides or methacrylamides,vinylpyridine, vinylpyrrolidone and vinyl-N-methylpyridinum, orcombinations thereof.
 13. The porous polymer microspheres according toclaim 10, wherein the functional groups have covalently bonded theretoor complexed therewith radioactive materials, biological materials, orligands for attaching radioactive materials or biological materials. 14.Porous polymer microspheres comprised of emulsion aggregated crosslinkedstyrene-acrylate polymer and having a size of from about 3 to about 50microns and a geometric standard deviation of about 1.25 or less.